Cost-effectiveness of metformin plus vildagliptin compared with metformin plus sulphonylurea for the treatment of patients with type 2 diabetes mellitus: a Portuguese healthcare system perspective

Figures & data

Figure 1. An overview of the model structure (adapted from UKPDS) used to estimate the cost-effectiveness of vildagliptin compared with sulphonylurea added on to metformin for the treatment of patients with type 2 diabetes mellitus from a Portuguese healthcare system perspective. HbA1c, glycated hemoglobin; QALY, quality-adjusted life-year, UKPDS, United Kingdom Prospective Diabetes Study.

Table 1. Baseline characteristics of the model cohort*.

Variable	Value
Age, mean (years)	63
Male (% patients)	52
Duration of T2D, mean (years)	9.13
Smokers (% patients)	21
Serum HbA1c, mean (%)	7.2
Systolic blood pressure (mm/Hg)	148
Serum TC:HDL ratio, mean	5:1
BMI, mean (kg/m^2)	31.39

BMI, body mass index; HbA1c, glycated hemoglobin; HDL, high-density lipoprotein; T2D, type 2 diabetes; TC, total cholesterol.

*Data extracted from a cross-sectional study of 2434 T2D patients who received pharmacological treatment in Portugal24.

Table 2. Main efficacy and safety parameters of modeled interventions.

Variable	Value		Reference	Value		Reference
	MET + SU	MET + VIL		MET + basal insulin	MET + intensive insulin
HbA1c reduction, Year 1 (%)	−0.53	−0.44	10	−1.1	−1.1	38
Coefficient of failure* (%)	0.37	0.20		0.2†	0.2†
Hypoglycemia (%)	16.2	1.7		16.2	16.2	38
Severe hypoglycemia (%)	0.72	0		3.3	3.3	38
Weight gain (kg/year)	1.56	−0.23		1.7	1.7	38
Change in TC:HDL (%/year)	−2.37†	−5.18†		–	–	–

HbA1c, glycated hemoglobin; HDL, high-density lipoprotein; MET, metformin; SU, sulphonylurea; TC, total cholesterol; VIL, vildagliptin.

*Coefficient of failure was defined as the slope of the least-squares regression line of HbA1c vs time from Week 24 to Week 52 of Year 1 of a head-to-head clinical trial of metformin plus vildagliptin vs metformin plus sulphonylurea10.

†Novartis, unpublished data.

Table 3. Annual cost of treatment in patients with T2D.

Treatment	Cost (€)	References
MET + generic SU	76.70	39,40
MET + vildagliptin	662.74	39,40
MET + basal-bolus insulin regimen	515.00	39,40
MET + multiple-dose insulin regimen	763.37	39,40
Insulin regimen monitoring costs	542.62	41,42

MET, metformin; SU, sulphonylurea; T2D, type 2 diabetes.

Table 4. Costs of complications.

Event	Cost per event (€)		Reference
	First year	Maintenance
Ischemic heart disease	1889.52	720.66*	43
Myocardial infarction (non-fatal)	2402.55	865.64*	43
Congestive heart failure	3624.13	1484.81*	43
Stroke (non-fatal)	3963.98	1177.34*	43
Lower limb amputation	6437.06	2342.45*	43
Blindness in one eye	11,736.00	11,736.00	44
Renal failure	29,354.00	29,354.00^†	43
Hypoglycemia	371.00	–	45
Severe hypoglycemia	1370.00	–	45
Myocardial infarction (fatal)	3185.44	–	43
Stroke (fatal)	4852.95	–	43

*Values calculated from first-year values using proportion presented by Clarke et al.46.

^†Weighted approach based on surgical diagnosis-related groups for renal failure (2008–2010) plus the estimated cost per patient for hemodialysis (2010).

Table 5. Number of diabetes-related events: 10,000 simulations over a lifetime time horizon.

Diabetes complication	MET + SU	MET + VIL	Difference
Macrovascular events*	5931 (2409)	5876 (2292)	−55 (−117)
Microvascular events†	884 (386)	876 (339)	−8 (−47)
Deaths‡	10,000 (2149)	10,000 (2089)	0 (−60)
Total non-fatal diabetes-related adverse events	6815 (2795)	6752 (2631)	−63 (−164)

MET, metformin; SU, sulphonylurea; VIL, vildagliptin.

All values are per cohort; values in parentheses were obtained at 5 years of the model run.

*Macrovascular events included ischemic heart disease, myocardial infarction (non-fatal), congestive heart failure, and stroke.

†Microvascular events included amputation, blindness in one eye, and renal failure.

‡Deaths included both diabetes-related and non-diabetes-related deaths.

Table 6. Base-case analysis: 10,000 simulations over a lifetime time horizon.

	MET + SU	MET + VIL	Difference
Cost of comorbidities, mean (€)	7400	7224	−177
Cost of side effects, mean (€)	715	422	−293
Cost of drug acquisition, mean (€)	2837	4785	+1948
Cost of monitoring, mean (€)	2297	1978	−383
Total cost, mean (€)	13,248	14,409	+1161
Life years, mean	7.6591	7.7486	+0.0896
QALYs, mean	5.6401	5.7681	+0.1279
ICER (€/QALY)	–	–	+9072

ICER, incremental cost-effectiveness ratio; MET, metformin; QALY, quality-adjusted life-year; SU, sulphonylurea; VIL, vildagliptin.

All costs and QALYs are mean values per patient and are discounted.

Figure 2. Cost-effectiveness acceptability curve. ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life-year.

Cabrita J, Lopes MM, de Oliveira Martins S, et al. Perfil de prescriçäo e avaliaçäo do grau de cumprimento de orientaçöes terapêuticas em diabéticos tipo 2: Estudo transversal em medicina geral e familiar. Rev Port Farmacoter 2011;3:7-13

 Google Scholar

Ferrannini E, Fonseca V, Zinman B, et al. Fifty-two-week efficacy and safety of vildagliptin vs. glimepiride in patients with type 2 diabetes mellitus inadequately controlled on metformin monotherapy. Diabetes Obes Metab 2009;11:157-66

 PubMed Web of Science ®Google Scholar

Monami M, Marchionni N, Mannucci E. Long-acting insulin analogues versus NPH human insulin in type 2 diabetes: a meta-analysis. Diabetes Res Clin Pract 2008;81:184-9

 PubMed Web of Science ®Google Scholar

IMS Health. IMS Health Moving Annual Target (MAT) for Antidiabetics in Portugal from June 2012 to June 2013. Porto Salvo: IMS Health, 2013

 Google Scholar

Infarmed. Autoridade Nacional do Medicamento e Produtos de Saúde I.P. Lisbon, 2014

 Google Scholar

Ministérios da Economia e do Emprego e da Saúde. Despacho no. 4294-A/2013. Ministérios da Economia e do Emprego e da Saúde. Lisbon, 2013

 Google Scholar

Pereira R, Gouveia M, Martins AP. Análise custo-efectividade de sitagliptina quando adicionada e metformina em doentes com diabetes tipo 2 em Portugal. Revista Portuguesa de Diabetes 2012;7:13-23

 Google Scholar

Ministério da Saúde. Portaria 163. Portaria n.° 163. (2013) Diário da República. Lisbon, 2013

 Google Scholar

Portugal S, Martins B, Ramos L, et al. Estudo de Avaliação do Impacto dos Custos Financeiros e Sociais da Deficiência. Relatório Final. Coimbra: Centro de Estudos Sociais, Instituto Nacional de Reabilitação, Ministério do Trabalho e da Solidariedade Social, 2010

 Google Scholar

Hammer M, Lammert M, Mejias SM, et al. Costs of managing severe hypoglycaemia in three European countries. J Med Econ 2009;12:281-90

 PubMedGoogle Scholar

Clarke P, Gray A, Legood R, et al. The impact of diabetes-related complications on healthcare costs: results from the United Kingdom Prospective Diabetes Study (UKPDS Study No. 65). Diabet Med 2003;20:442-50

 PubMed Web of Science ®Google Scholar